Abstract:

Objective To analyze the relationship between miR-506-3p and immune microenvironment characteristics and platinum chemotherapy sensitivity in patients with epithelial ovarian cancer （EOC）. Methods A total of 87 EOC patients admitted to General Hospital of Central Theater Command， People's Liberation Army of China from June 2021 to June 2023 were selected as the study subjects. According to the chemotherapy efficacy， the patients were divided into a sensitive group （n=57） and a drug-resistant group （n=30）. The expression of miR-506-3p in EOC tissues and adjacent tissues was compared. The relationships between the expression of miR-506-3p in EOC tissues and the clinicopathological characteristics， immune microenvironment characteristics [levels of T cell subsets CD4⁺， CD8⁺， helper T （Th） 17 cells， and regulatory T （Treg） cells， as well as the ratio of CD4⁺/CD8⁺ and the ratio of Treg cells /Th17 cells] and chemotherapy sensitivity to platinum drugs were analyzed. The relationship between the platinum chemotherapy sensitivity in EOC patients of the sensitive group and the drug-resistant group and the clinicopathological characteristics， immune microenvironment characteristics， and miR-506-3p expression was analyzed. A generalized additive model （GAM） was used to analyze the relationship between the expression of miR-506-3p and immune microenvironment-related indicators. A multivariate logistic regression model was used to conduct an independent correlation analysis and subgroup internal correlation analysis of miR-506-3p expression and the platinum chemotherapy sensitivity. A restricted cubic spline logistic regression model was established to analyze the dose-response relationship between miR-506-3p expression and the platinum chemotherapy sensitivity in patients with EOC. Results The expression level of miR-506-3p in the EOC tissues （0.33±0.09） was significantly lower than that in the adjacent tissues （1.12±0.40）， with a statistically significant difference （t=19.05，P<0.001）. According to the average expression level of miR-506-3p （0.33）， the EOC patients were divided into a high-expression group （n=42） and a low-expression group （n=45）. There were statistically significant differences in the immune microenvironment characteristics [CD8⁺ T cells （t=2.91， P=0.006）， Th17 cells （t=3.69，P=0.001）， Treg cells （t=3.12，P=0.003）， Treg cells/Th17 cells ratio （t=4.23，P<0.001）] and platinum chemotherapy sensitivity （χ²=18.32，P<0.001） between the low-expression group and the high-expression group. Compared with the sensitive group， the proportions of age≥55 years old （χ²=4.74， P=0.029）， FIGO stage Ⅲ-Ⅳ （χ²=6.11， P=0.013）， BRCA mutation rate （χ²=9.47， P=0.002）， T cell subsets CD8⁺ level （t=5.57， P<0.001）， Th17 cell level （t=6.50， P<0.001） in the drug-resistant group were significantly increased， while T cell subsets CD4⁺ level （t=2.48， P=0.015）， CD4⁺/CD8⁺ ratio （t=3.36， P=0.001）， Treg cells level （t=5.26， P<0.001）， Treg cells/Th17 cells ratio （t=4.39， P<0.001）， and miR-506-3p expression level （t=8.99， P<0.001） were significantly decreased， with statistically significant differences. GAM analysis results showed that the immune microenvironment indicators CD4⁺ T cells level （F=7.34，P<0.001）， CD8⁺ T cells level （F=4.58， P<0.001）， CD4⁺/CD8⁺ ratio （F=2.03， P=0.005）， Th17 cells level （F=6.17， P<0.001）， Treg cells level （F=1.98， P=0.009）， and Treg cells/Th17 cells ratio （F=2.71， P=0.002） were all correlated with the expression of miR-506-3p. The results of multivariate logistic regression analysis showed that the expression of miR-506-3p in EOC tissues was independently correlated with platinum chemotherapy sensitivity （P<0.001）. Subgroup analysis showed that in EOC patients with different ages and maximum diameter of residual lesion， the relationship between miR-506-3p expression in EOC tissues and platinum chemotherapy sensitivity was stable， and there was no interaction between subgroups. Restricted cubic spline model analysis showed that the risk of chemotherapy resistance to platinum drugs decreased with the increase of miR-506-3p expression level. Conclusions The expression level of miR-506-3p in EOC tissues is related to the immune microenvironment of patients and can regulate the balance of CD4⁺ and CD8⁺ T cells as well as Th17 and Treg cells. The expression of miR-506-3p is independently and stably associated with the sensitivity of EOC patients to platinum-based chemotherapy. Its increase can reduce the risk of chemotherapy resistance and is expected to become a potential biomarker for evaluating the immune status of EOC patients and predicting the efficacy of platinum-based chemotherapy.

Key words: Carcinoma， ovarian epithelial, miR-506-3p, Immune microenvironment, Chemotherapy sensitivity